Astrocytes provide the temporal dynamic required for theta-driven memory formation in the hippocampus

Theta oscillations (4-12 Hz) in the hippocampus are caused by the synchronous bursting activity of neuronal populations. They are critical for grouping and selecting neuronal ensembles in the context of spatial navigation, memory, and learning, but the reason why this frequency band is particularly effective for adjusting neuronal ensembles remains speculative. Here we show that burst activity at the CA3-CA1 synapse of the mouse hippocampus leads to a rapid activation of astrocytic leaflets possibly via the retrograde release of endocannabinoids that activate transient receptor potential channels expressed by astrocytes. This in turn, potentiates the release of transmitter from Schaffer collaterals. We demonstrate that this mechanism is synapse specific and is necessary for the induction of long-term potentiation. Strikingly, this positive feedback loop peaks 50 to 200 ms post-burst, i.e., a timing optimal for the specific reinforcement of neuronal activity occurring in the theta range. Our results suggest that astrocytes provide the specific timing for the potentiation of synaptic transmission occurring during the initial steps of learning and memory processes.